Jean-Philippe Couderc

Surgical ablation of atrial fibrillation during mitral-valve surgery

BACKGROUND Among patients undergoing mitral-valve surgery, 30 to 50% present with atrial fibrillation, which is associated with reduced survival and increased risk of stroke. Surgical ablation of atrial fibrillation has been widely adopted, but evidence regarding its safety and effectiveness is limited. METHODS We randomly assigned 260 patients with persistent or long-standing persistent atrial fibrillation who required mitral-valve surgery to undergo either surgical ablation (ablation group) or no ablation (control group) during the mitral-valve operation. Patients in the ablation group underwent further randomization to pulmonary-vein isolation or a biatrial maze procedure. All patients underwent closure of the left atrial appendage. The primary end point was freedom from atrial fibrillation at both 6 months and 12 months (as assessed by means of 3-day Holter monitoring). RESULTS More patients in the ablation group than in the control group were free from atrial fibrillation at both 6 and 12 months (63.2% vs. 29.4%, P<0.001). There was no significant difference in the rate of freedom from atrial fibrillation between patients who underwent pulmonary-vein isolation and those who underwent the biatrial maze procedure (61.0% and 66.0%, respectively; P=0.60). One-year mortality was 6.8% in the ablation group and 8.7% in the control group (hazard ratio with ablation, 0.76; 95% confidence interval, 0.32 to 1.84; P=0.55). Ablation was associated with more implantations of a permanent pacemaker than was no ablation (21.5 vs. 8.1 per 100 patient-years, P=0.01). There were no significant between-group differences in major cardiac or cerebrovascular adverse events, overall serious adverse events, or hospital readmissions. CONCLUSIONS The addition of atrial fibrillation ablation to mitral-valve surgery significantly increased the rate of freedom from atrial fibrillation at 1 year among patients with persistent or long-standing persistent atrial fibrillation, but the risk of implantation of a permanent pacemaker was also increased. (Funded by the National Institutes of Health and the Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT00903370.).

Electrocardiographic identification of drug-induced QT prolongation: assessment by different recording and measurement methods.

Background: Careful assessment of QT interval prolongation is required before novel drugs are approved by regulatory authorities. The choice of the most appropriate method of electrocardiogram (ECG) acquisition and QT/RR interval measurement in clinical trials requires better understanding of the differences among currently available approaches. This study compared standard and Holter‐derived 12‐lead ECGs for utility in detecting sotalol‐induced QT/QTc and RR changes. Manual methods (digitizing pad and digital on‐screen calipers) were compared for precision of QT and RR interval measurement.

Effects of on-road highway aerosol exposures on autonomic responses in aged, spontaneously hypertensive rats.

Epidemiological studies associate ambient particulate pollution with adverse health outcomes in elderly individuals with cardiopulmonary diseases. We hypothesized that freshly generated ultrafine particles (UFP) contribute to these effects, as they are present in high number concentrations on highways and vehicle passengers are exposed directly to them. Aged spontaneously hypertensive rats (9–12 mo) with implanted radiotelemetry devices were exposed to highway aerosol or filtered, gas-denuded (clean) air using an on-road exposure system to examine effects on heart rate (HR) and heart-rate variability (HRV). On the day of exposure, rats were pretreated with low-dose inhaled or injected lipopolysaccharide (LPS) to simulate respiratory tract or systemic inflammation, respectively. Exposures (6 h) in compartmentalized whole-body chambers were performed in an air conditioned compartment of a mobile laboratory on I-90 between Rochester and Buffalo, NY. HRV parameters were calculated from telemetric blood pressure signals and analyzed for the baseline period and for the first 32 h postexposure. The aerosol size (count median diameter = 15–20 nm; geometric standard deviation = 1.4–4.3) and number concentration (1.95–5.62 × 105/cm3) indicated the predominance of UFP. Intraperitoneal LPS significantly affected all of the parameters in a time-dependent manner; response patterns after inhaled or injected LPS pretreatment were similar, but more prolonged and greater in LPS-injected rats. A significant effect of highway aerosol was found, irrespective of pretreatment, which resulted in decreased HR in comparison to clean air-exposed rats. This effect was more persistent (∼ 14 h) in those rats that received ip LPS as compared to saline. The highway aerosol also significantly affected short-term alterations in autonomic control of HR, as evidenced by elevations in normalized high frequency power and decreased vagosympathetic balance. These findings show that environmental exposure concentrations of mixed traffic-related UFP/gas-phase emissions can affect the autonomic nervous system.

Changes in deceleration capacity of heart rate and heart rate variability induced by ambient air pollution in individuals with coronary artery disease.

Background and ObjectiveExposure to ambient particles has been shown to be responsible for cardiovascular effects, especially in elderly with cardiovascular disease. The study assessed the association between deceleration capacity (DC) as well as heart rate variability (HRV) and ambient particulate matter (PM) in patients with coronary artery disease (CAD).MethodsA prospective study with up to 12 repeated measurements was conducted in Erfurt, Germany, between October 2000 and April 2001 in 56 patients with physician-diagnosed ischemic heart disease, stable angina pectoris or prior myocardial infarction at an age of at least 50 years. Twenty-minute ECG recordings were obtained every two weeks and 24-hour ECG recordings every four weeks. Exposure to PM (size range from 10 nm to 2.5 μm), and elemental (EC) and organic (OC) carbon was measured. Additive mixed models were used to analyze the association between PM and ECG recordings.ResultsThe short-term recordings showed decrements in the high-frequency component of HRV as well as in RMSSD (root-mean-square of successive differences of NN intervals) in association with increments in EC and OC 0-23 hours prior to the recordings. The long-term recordings revealed decreased RMSSD and pNN50 (% of adjacent NN intervals that differed more than 50 ms) in association with EC and OC 24-47 hours prior to the recordings. In addition, highly significant effects were found for DC which decreased in association with PM2.5, EC and OC concurrent with the ECG recordings as well as with a lag of up to 47 hours.ConclusionsThe analysis showed significant effects of ambient particulate air pollution on DC and HRV parameters reflecting parasympathetic modulation of the heart in patients with CAD. An air pollution-related decrease in parasympathetic tone as well as impaired heart rate deceleration capacity may contribute to an increased risk for cardiac morbidity and sudden cardiac death in vulnerable populations.

QT interval variability in body surface ECG : measurement, physiological basis, and clinical value: position statement and consensus guidance endorsed by the European Heart Rhythm Association jointly with the ESC Working Group on Cardiac Cellular Electrophysiology

This consensus guideline discusses the electrocardiographic phenomenon of beat-to-beat QT interval variability (QTV) on surface electrocardiograms. The text covers measurement principles, physiological basis, and clinical value of QTV. Technical considerations include QT interval measurement and the relation between QTV and heart rate variability. Research frontiers of QTV include understanding of QTV physiology, systematic evaluation of the link between QTV and direct measures of neural activity, modelling of the QTV dependence on the variability of other physiological variables, distinction between QTV and general T wave shape variability, and assessing of the QTV utility for guiding therapy. Increased QTV appears to be a risk marker of arrhythmic and cardiovascular death. It remains to be established whether it can guide therapy alone or in combination with other risk factors. QT interval variability has a possible role in non-invasive assessment of tonic sympathetic activity.

ECG features of microvolt T-wave alternans in coronary artery disease and long QT syndrome patients

UNLABELLED T-wave alternans (TWA) is a marker of myocardial electrical instability. We compared ECG features of microvolt TWA in coronary artery disease (CAD) and long QT syndrome (LQTS) patients. METHOD The study populations consisted of 43 CAD and 39 LQTS patients. TWA was detected in resting Holter recordings using the new correlation method (CM). After preprocessing to adjust for RR variability and respiratory modulation, CM was used to quantify TWA amplitude (A(CM)), duration (N(CM)), and magnitude (MAG(CM); defined as the product of A(CM) and N(CM)). RESULTS TWA was detected in 19 (44%) CAD and 17 (44%) LQTS patients. TWA was associated with longer RR intervals (P = 0.006) and had larger magnitudes (P = 0.067) in LQTS than CAD patients. The TWA was identified as transient (nonstationary) in 15 of 19 (79%) TWA-positive CAD patients, and in 8 of 17 (47%) TWA-positive LQTS patients (P = 0.047). CONCLUSIONS The frequency of TWA detected with CM is similar in LQTS and CAD patients. TWA is larger in LQTS than in CAD patients, whereas TWA is more frequently transient (nonstationary) in LAD than LQTS patients. In LQTS patients, but not in CAD patients, a longer RR is associated with TWA, indicating different electrophysiologic mechanisms in the two pathologies.

Beat-to-Beat Repolarization Variability in LQTS Patients with the SCN5A Sodium Channel Gene Mutation

Current techniques evaluating beat‐to‐beat variability of repolarization rely on accurate determination of T wave endpoints. This study proposes a T wave endpoint‐independent method to quantify repolarization variability in a standard 12‐lead ECG using a wavelet transformation. Our method was used to identify repolarization variability in long QT syndrome patients (LQTS) with the SCN5A sodium channel gene mutation. Using wavelet transformations based on the second Gaussian derivative, we evaluated repolarization variability in 11 LQTS patients with the mutation, 13 noncarrier family members, and 28 unrelated healthy subjects. Time‐domain repolarization variability parameters (SDRTo, SDRTm) and wavelet parameters describing temporal (beat‐to‐beat) variability of repolarization in time (TVT) and in amplitude (TVA) were analyzed. Reproducibility of wavelet parameters and relationship of wavelet‐based variability with heart rate and preceding RR interval were investigated. The wavelet‐based method quantified beat‐to‐beat variability of the entire repolarization segment (regardless of QT interval identification) providing insight into variability in repolarization morphology. Our method showed that SCN5A carriers have significantly increased repolarization variability in amplitude (23%± 14% vs 8 ± 4%, P < 0.001) and in time (14 ± 17 ms vs 3 ± 2 ms, P < 0.004) compared to noncarriers. Variability of repolarization amplitude was found to be heart rate dependent with variability decreasing with increasing heart rate. Relative error describing reproducibility of TVA and TVT was ± 5% and ± 10%, respectively. Our method quantifies repolarization variability in amplitude and in time without the need to identify T or U wave endpoints. Wavelet‐detected repolarization variability contributes to phenotypic identification of SCN5A carriers, with more pronounced beat‐to‐beat variability in repolarization amplitude than in time.

The telemetric and holter ECG warehouse initiative (THEW): A data repository for the design, implementation and validation of ECG-related technologies

we present an initiative supported by the National Heart Lung, and Blood Institute and the Food and Drug Administration for the development of a repository containing continuous electrocardiographic information to be shared with the worldwide scientific community. We believe that sharing data reinforces open scientific inquiry. It encourages diversity of analysis and opinion while promoting new research and facilitating the education of new researchers.

Assessment of the stability of the individual-based correction of QT interval for heart rate.

Background: Modeling the relationship between QT intervals and previous R‐R values remains a challenge of modern quantitative electrocardiography. The technique based on an individual regression model computed from a set of QT–R‐R measurements is presented as a promising alternative. However, a large set of QT–R‐R measurements is not always available in clinical trials and there is no study that has investigated the minimum number of QT–R‐R measurements needed to obtain a reliable individual QT–R‐R model. In this study, we propose guidelines to ensure appropriate use of the regression technique for heart rate correction of QT intervals.

Analyses of Dynamic Beat-to-Beat QT-TQ Interval (ECG Restitution) Changes in Humans under Normal Sinus Rhythm and Prior to an Event of Torsades de Pointes during QT Prolongation Caused by Sotalol

Background: Restitution through intracardiac pacing has been used to assess arrhythmia vulnerability. We examined whether analyses of sequential beat‐to‐beat QT and TQ interval measures can be used to quantify ECG restitution changes under normal sinus rhythm.